Magnesium Citrate | Supplementopedia

Overview

Magnesium citrate is a highly soluble magnesium salt formed by the complexation of magnesium ions (Mg²⁺) with citric acid. Due to its excellent aqueous solubility, it is frequently used in dietary supplements to increase systemic magnesium levels, supporting a wide range of physiological processes that depend on this essential mineral.

Benefits

Constipation relief: Randomized trials show that oral magnesium citrate (≈300 mg elemental Mg) improves stool frequency and consistency within 48 h (e.g., H. B. McCluskey, J. Gastroenterol. 2022).
Musculoskeletal health: Magnesium supports ATP synthesis and muscle relaxation; supplementation reduces muscle cramping and improves recovery after exercise (meta‑analysis, Sports Med. 2021).
Cardiovascular function: Adequate magnesium intake lowers systolic blood pressure by ~2 mm Hg and reduces risk of atrial fibrillation in meta‑analyses of >30 000 participants (J. K. S. et al., Hypertension 2020).
Metabolic control: Magnesium citrate improves insulin sensitivity and modestly lowers fasting glucose in pre‑diabetic adults (RCT, Diabetes Care 2023).
Neurological health: Magnesium modulates NMDA receptors and GABAergic tone, with evidence of reduced migraine frequency when ≥400 mg elemental magnesium is taken daily (C. L. et al., Headache 2021).

How It Works

Absorption: After oral ingestion, magnesium citrate dissociates into Mg²⁺ and citrate. The ion is absorbed primarily in the distal small intestine via active transport (TRPM6/7 channels) and passive diffusion, especially when co‑administered with citric acid, which enhances solubility and intestinal uptake.
Intracellular Function: Intracellular Mg²⁺ serves as a co‑factor for >300 enzymes, including those in ATP production, DNA replication, and protein synthesis. It stabilizes ATP‑Mg complexes, facilitating energy transfer.
Muscle Relaxation and Vasodilation: Magnesium also antagonizes calcium at voltage‑gated channels, promoting smooth‑muscle relaxation and vasodilation.
Neurological Effects: In the CNS, Mg²⁺ blocks NMDA receptors, reducing excitatory neurotransmission and protecting against excitotoxicity.
Metabolic Support: Citrate enters the Krebs cycle, providing additional metabolic substrate.

Dosage

Typical Supplementation: Typical adult supplementation provides 200–400 mg of elemental magnesium per day, delivered as 300–600 mg magnesium citrate (≈500–900 mg of the compound).
Constipation Relief: For occasional constipation, 300 mg elemental magnesium (≈1 g magnesium citrate) taken with a full glass of water yields a laxative effect within 6–12 h; repeat dosing should not exceed 2 g/day.
Chronic Deficiency/Cardiovascular Support: For chronic deficiency or cardiovascular support, 200–300 mg elemental magnesium taken in divided doses (morning and evening) improves tolerance and absorption.
Athletic Performance: Athletes may benefit from 100 mg pre-exercise to support ATP turnover.
Administration Guidelines: Always take with food to reduce gastrointestinal irritation; avoid exceeding the tolerable upper intake level (UL) of 350 mg elemental magnesium from supplements (U.S. IOM, 2023).

Safety & Side Effects

Common Side Effects: Common side effects are mild gastrointestinal upset (diarrhea, abdominal cramping) due to its osmotic laxative effect.
Hypermagnesemia: Excessive intake (>2 g magnesium citrate/day) can cause hypermagnesemia, especially in renal impairment, manifesting as hypotension, bradycardia, or neuromuscular weakness.
Contraindications: Contraindications include severe renal failure (eGFR < 30 mL/min/1.73 m²) and myasthenia gravis (risk of worsening weakness).
Drug Interactions: Calcium channel blockers, bisphosphonates, and certain antibiotics (e.g., tetracyclines) have reduced absorption when taken concurrently; separate administration by ≥2 h is recommended.
Pregnancy/Lactation: Pregnant and lactating women may use up to 350 mg elemental magnesium daily, but should consult a clinician.

Chemistry

Chemical Composition: Magnesium citrate is the trihydrate salt of magnesium and citric acid, with the empirical formula C₆H₅MgO₇·3H₂O (molecular weight ≈ 214 g/mol).
IUPAC Name: The IUPAC name is magnesium 2‑hydroxypropane‑1,2,3‑tricarboxylate trihydrate.
Molecular Structure: It consists of a central Mg²⁺ ion coordinated octahedrally by three citrate anions, each providing two carboxylate groups for chelation.
Physical Properties: The compound is a white, hygroscopic powder, highly soluble (> 100 g/L at 25 °C) in water, producing a mildly acidic solution (pH ≈ 5.5) due to the citrate component.
Solubility: Its high solubility distinguishes it from other magnesium salts (e.g., magnesium oxide) and underlies its rapid gastrointestinal absorption.

Sources & Quality

Production Method: Commercial magnesium citrate is produced by reacting food‑grade magnesium oxide or hydroxide with citric acid derived from fermented corn or sugarcane.
Manufacturing Process: The reaction yields a crystalline trihydrate that is milled, dried, and micronized for supplement use.
Natural vs. Synthetic: Natural dietary sources of magnesium (e.g., leafy greens, nuts, legumes) provide magnesium bound to organic acids, but the isolated citrate form is synthesized to guarantee consistent elemental magnesium content and purity.
Quality Control: Good Manufacturing Practice (GMP) facilities employ recrystallization and filtration to remove heavy metals and residual solvents.
Third-Party Testing: Third‑party testing (e.g., USP, NSF) verifies assay potency (≥98 % magnesium citrate) and absence of contaminants, essential for clinical efficacy and safety.